TREATMENT OF PREMATURE EJACULATION

Abstract

The invention relates to methods and compositions for treating premature ejaculation in a male or prolonging intercourse comprising administering to the male an antidepressant via a route selected from the group consisting of mucosal administration (preferably nasal, buccal or rectal), administration to the lungs (preferably by inhalation), local administration to at least a part of the male genitalia (applied to the penis far example, in the form of a gel) and combinations thereof.

Full Text

Field of the Invention
The invention relates to methods and compositions for the treatment of male
sexual dysfunction, and particularly to the treatment of premature ejaculation.
Background Art
Mechanical devices have been previously employed in attempts to prevent
premature ejaculation. Such devices operate by reducing the stimulation of the penis,
but are often awkward and uncomfortable and may not be particularly effective in
desensitising the most sensitive part of the penis which is the glans.
Antidepressants have been administered orally, in tablet form, to treat premature
ejaculation, although there are significant side effects with this approach. In particular,
antidepressants can fead to nausea, vomiting and diziness. Furthermore, their effects are
very sensitive to the amount and timing of food and alcohol ingested, as well as the
amount of fat on. the patient so their effects can "be unpredictable.
Premature ejaculation has been treated in the past by the topical application of
compositions containing local anaesthetics, such as Udocaine, to the skin of the peois to
reduce sensitivity.
One limitation of such a method of treatment is that the composition must be
substantially removed from the slrin prior to intercourse to avoid transferring the
anaesthetic to a female partner, thereby reducing reduced vaginal sensitivity.
Overapplication of the topical anaesthetic composition is also possible, leading to
substantially diminished enjoyment of intercourse by the male.
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Any discussion of the prior art throughout the specification, should in no way be
considered as an. admission, "that such, prior art is widely known or forms part of Gommoa
general knowledge in the field.
It is an object of the present invention to overcome or ameliorate at least one of the
abovementioned disadvantages of using conventional anaesthetics.
Description of the Invention.
According to a first aspect, the invention provides a method of treating premature
ejaculation in a male comprising administering to the male an antidepressant via a route
selected from the group consisting of i) nucosal administration, ii) administration to the
lungs iii) local administration to the male genitalia, and iv) a combination of two or more
of mucosal administration, administration to the lungs and local administration to the
male genitalia.
Preferably, the mucosal administration is nasal administration although it may also
be via other mucosal routes such as buccal administration or rectal administration.
Preferably, administration to the lungs is by way of inhalation.
Preferably, the local administration is directly to tlie penis.
Specifically, the antidepressant or a combination of antidepressants is administered
by one of the abovementioned routes alone or by a combination of mucosal (preferably
nasal) and topical (preferably to the penis), orby a combination of mucosal (preferably
nasal) and lung (preferably by inhalation), or by a combination of topical (preferably to
the pesns) and hmg (preferably by inhaletion), or even by a combination of all there, ie a
combination of topical (preferably to the penis), mucosal (preferably nasal) and lung
(preferably by inhalation) administration.
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The most preferred single modes of administration are nasal, to the lungs, and
buccal. The most preferred combination modes of administration are combinations of
nasal and to the penis, lungs and to the penis, and buccal and to the penis.
For example, the treatment of the present invention maybe administered by way of
a nasal spray, an inhaler or a troche, either alone or in combination with a suitable
formulation applied to the penis. In combination therapies, the same or different
antidepressants maybe administered via different routes.
Without wishing to be bound by theory, it is believed the routes of the present
invention allow the drugs to bypass the first metabolism of the liver, and cross the
blood/brain barrier to act straight away on tbe brain. Tins mode of action, may serve to
explain the small doses used to achieve success, the rapid onset of action and the
consistency in dose/response patterns.
The combination of topical (to the penis) and the mucosal routes above appear to
result in a synergistic enhancement of the effect in preventing premature ejaculation.
According to a second aspect, the invention provides a method of treating
premature ejaculation in a male comprising the step of administering to the male an
antidepressant, wherein said antidepressant is administered via a route selected from the
group consisting of i) nasal administration, ii) administration to the lungs, iii) buccal
administration, iv) administration to the penis and v) a combination of two or more of
nasal administration, administration to the lungs, buccal administration and local
administration to the penis.
Surprisingly, the present inventor has found that antidepressants administered by
these routes result in a sufficient degree of anaesthesia to tie penis to overcome
premature ejaculation.
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The term antidepressant as used hereto refers to any substance used in the
treatment of clinical depression. All antidepressants are believed to be suitable for use in
the present invention.
In one preferred embodiment the antidepressant is a selective serotonin reuptake
inhibitor (known as an SSRI).
In alternative preferred embodiments the antidepressant is a bicyclic, tricychic or
tetracyclic antidepressant.
In yet another alternative preferred embodiment, the antidepressant is a
monoamine oxidase inhibitor.
In further alternative preferred embodiments, the antidepressant may be selected
from one of the following classes: Serotonin Norepinephriwe Reuptake Inhibitors,
Norepinephrine Dopamine Reuptake Inhibitors, Serotonin Antagonist and Reuptake
Inhibitors, Norepinephrine Antagonist/Serotonin Antagonists, Monoamine Oxidases
(MAO) inhibitors, synthetically derived phenylpiperaznie antidepressants, antagonists of
central L2-a2 auto and heteroadrenoceptors.
As mentioned, the inventor has found that an antidepressant agent, that is an agent
that is more typically used for the treatment of clinical depression, is capable of delaying
ejaculation when administered by nasal/lung/buccal or a combination of these, or In
combination with administration, tp the penis, while minimising side effects typical of
such antidepressants such as vomitmg nausea and dizziness.
Further, the agent can be administered at a fraction of the dose than is usually used
to treat depression, wife rapid onset of action and -with. a. high degree of predictability.
Importantly, for the treatment of premature ejaculation, the inventor has found that
when topically applied to at least a portion of the skin of the male genitalia, for example,

when applied to the penis, an antidepressant agent will induce a sufficient degree of
anaesthesia to provide an improvement to the condition of premature ejaculation.
Even more surprisingly, it has been found that administering antidepressants
mucosally, preferably nasally, or by administration to the lungs, delays ejaculation
during intercourse.
A combination of mucosal, preferably nasal, and local administration has been
found to be extremely useful in preventing premature ejaculation and prolonging sexual
intercourse.
Alternatively, a combination of administration to the lungs, and local
administration, has been found to be extremely useful in preventing premature
ejaculation and prolonging sexual intercourse.
A further combination of routes of administration, namely a combination of
mucosal, preferably nasal, and administration to the lungs has also been found to be
valuable in preventing premature ejaculation and prolonging sexual intercourse.
One or more antidepressants may be used in combination, and they may be used
alone or with one or more carriers for facilitating the application of the antidepressant
agent to the skin or too the mucosa.
If a combination of two or more routes selected from mucosal administration,
administration to the lungs and local administration is used, then the same antidepressant
or antidepressant combination may be administered by the two or more different routes,
or different antidepressants or combinations of antidepressants may be administered by
the two or more different routes.
According to a third aspect, the invention provides a composition for the treatment
of premature ejaculation, said composition comprising an antidepressant formulated for
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mucosal administration. More preferably, the antidepressant is formulated for nasal
administration.
According to a fourth aspect, the invention provides a composition for the
treatment of premature ejaculation, said composition comprising an antidepressant
formulated for administration to the lungs. Most preferably, administration to the lungs
is by inhalation.
According to a fifth aspect, the invention provides a composition including an
antidepressant formulated for local administration to the male genitatia.
According to a sixth aspect, the invention provides a kit, said kit comprising an
antidepressant formulated for nasal administration and an antidepressant formulated for
topical application. Preferably, the antidepressants are selected such that a synergistic
interaction occurs when there is a combination of nasal and local administration.
According to a seventh aspect, the invention provides a kit, said kit comprising an
antidepressant formulated for administration to the lungs and an antidepressant
formulated for topical application- Preferably, the arxtidepressants are selected such that
a synergistic interaction occurs when there is a combination of lung and Local
administration,
According to a eighth aspect, the invention provides a kit, said kit comprising an
antidepressant formulated for nasal administration and an antidepressant formulated for
application to the lungs. Preferably, the antidepressants are selected such that a
synergistic interaction occurs when there is a combination of nasal and lung
administration.
According to a ninth aspect, the invention provides a kit, said kit comprising an
antidspressant formulated for nasal administration, an antidepressant formulated for
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application to the lungs and an antidepressant formulated for topical administration..
Preferably, the antidepressants are selected such that a synergistic interaction.
According to a tenth aspect the invention provides a method of prolonging sexual.
intercourse involving a male, said method including the step of administering to said
male prior to intercourse an amount of an antidepressant effective to delay ejaculation:
and wherein said aatidepressant is administered via a route selected from the group
consisting of: mucosai administration, administration to the lungs, topical administration
to the male genitalia, and a combination of two or more of mucosai administration,
administration to the lungs or topical adiministration to the male genitalia.
According to an eleventh aspect the invention provides a method of prolonging
sexual intercourse involving a male and a. female, said method including the step of
administering to said male prior to intercourse an amount of an antidepressant effective
to delay ejaculation without anaesthetising the female genitalia; and wherein said
anntidepressant is administered via a route selected from the group consisting of: mucosai
administration, administration to the lungs, topical administration to the male genitalia,
and a combination of two or more of mucosai administration, administration to the lungs
or topical administration to the male genitalia.
Antideprcssants
As mentioned, any antidepressant is suitable for use in the present invention.
The antidepressants may be selected from:
• Selective Serotonin Reuptake Inhibitors (SSRI)
• Serotonin Norepinephrine Reuptake Inhibitors, (including bicyclic, tricyclic and
tetracyclic antidepiessants")
• Norepinephrine Dojpamine Reuptake Inhibitors
• Serotonin Antagonist and Renptake Inhibitors
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• Norepinephrine Antagonist/Serotonin Antagonists
• Monoatnine Oxidases (MAO) Inhibitors
• Synthetically derived phenylpiperazine antidepressants
• antagonists of central L2-a2 auto and heteroadrenoceptors
Some specific non-limiting examples of antidepressants include, but are not
limited to paroxetine, fluoxoetine and sertraline. Paroxetine may be formulated as a
hydrochloride (such as Aropax) or in the form, of other salts or in combination with other
bases such as mesylates, Other suitable antidepressants for use in the present invention
include citalopram hydrobromide (Cipramil), fluoxetine (Prozac), fluvoxamine (Luvox),
sertraline (Zoloft), nortriptyline hydrochloride (Allegron), clomipramine hydrocbloride
(Anafranil), dothiepin hydrochloride (Prothiaden), Imipramine hydrochloride (Tofranil),
mianserin hydrochloride (Tolvon), amitriptyline hydrochloride (Tryptanol), phenelzine
sulphate (Nardil), tranyicypromine sulphate (such as Parnate), isocarboxazid (Marplan),
moclobemide (Aurorix), serotonin and/or adrenalin update inhibitors such as venlafaxine
(Efexor), nefazodone hydrochloride (Serzone), trazodone (Desyrel), bupropion (Zyban),
mirtazapine (Remeron), doxepin hydrochloride (Sinequan) and trimipramine
(Surmontil).
Preferably, the antidepressant is administered in an amount of between 0.1 and
1 000mg per dose, depending upon the nature of active ingredient used and the seventy
of the patients problems, as well as other factors such as patient size. More preferably,
the dosage will be between 1 and l00mg antidepressant, even more preferably between 5
and 25 mg antidepressant. The exact dosage will be readily determined by a trained
clinician.
Topical Formulations
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For topically administered antidepressants, administration is typically by way of
application either to the skin of the region of the male genitalia as a composition that
may also include a carrier for facilitating the application of the antidepressant agent to
the skin.
Compositions may be applied to the male genitalia in the form of a gel, although
they may also be formulated as a lotion or a powder. It will be understood by those
skilled in the art that the particular form of the composition is not important, provided
that by contacting the composition with the skin in the male genital region, the
antidepressant agent is permitted to induce anaesthesia that that region.
The composition may be applied to any part of the male genitalia, such as the
penis only, or also to the scrotum or surrounding regions such as the perineum. Most
usually, a topical composition comprising an antidepressant is applied directly to the
penis.
The topical composition is typically applied by massaging into the skin for about
one minute, preferably about 30 to 60 minutes prior to intercourse.
Preferably, the concentration of the antidepressant in a composition is between
about 1 to 10% by weight, preferably about 3 to 6% by weight of the topical
composition.
Preferably, the antidepressant in the topical formulation is present in an amount of
between 0.1 and l000mg per dose, depending upon the active ingredient used. More
preferably, the dosage will be between 1 and 100mg antidepressant, even more
preferably between 5 and 25 mg antidepressant.
It will be understood by those skilled in the art that more than one type of agent
described above could be used in the composition of the invention, provided that the
composition is capable of introducing anaesthesia at a region of male genitalia either to
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which the composition is applied, or to the appropriate regions by means of mucosal
administration.
The composition may be provided in the form of a gel or lotion, or alternatively, it
may be provided as a powder which in use can be hydrated to form a gel or lotion
suitable for application to a region of male genitalia.
Most typically, the composition is applied to the skin of the male genitalia as a gel.
A. typical gel for facilitating application of the antidepressant is hydrogel such as
hydroxypropylmethylcellulose (Methocell EM4), or an acrylic acid polymer such as
Carbopol 943P. The polymer in the composition is present in the range of about 0.1 to
about 5 wt%. The carrier is typicaliy water soluble, non-irritating and does not sensitise
the skin. It is desirable if the carrier imparts a semi soft creamlike consistency to the
composition.
The topical compositions may further comprise an enhancer agent for enhancing
the absorption of the antidepresssnt agent through the skin. Examples of enhancer agent
include cyclodextrins such as a, b~, and g-cyclodextrin and 2-methylcyclodextrin.
Hydroxypropyl-b-cyclodextrin HPBCD is particularly advantageous as compositions
comprising HP BCD ace suitable for \ise vrith diabetic men. HPBCD is a cyclic polymer
having a ring shaped molecular structure including an inner cavity. It is understood that
an inclusion compound is formed with HPBCD which makes the antidepressant more
readily absorbed by the skin. The weight percent of the HPBCD in the composition is
preferably in the range of about 1 to 10 %.
HPBCD is a commercially available compound derived from b-cyclodextrin a
condensation with propylene oxide to provide the corresponding hydroxypxopyl
derivative having a degree of substitution of up to about 15 or higher. A degree of
substitution of about 5 to about 7 is preferred for compositions of the present invention.
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The antidepressant agent and the HPBCD are typically present in the composition
in a molar ratio of about 1:0.8 to 1:1.4 respectively. Preferably, the antidepressanl agent
and the HPBGD are present in a ratio of about 1:1.
The pHs of the compositions in the present invention are preferably in the range of
about 2 to about 8, and more preferably, around 7.4. The pH can be adjusted by any
physiologically suitable agent such as amoniumhydroxide or sodium hydroxide.
Other components of the composition may include water, monohydric and
polyhydric alcohols such as ethanol, polyethylene glycol, propylene glycol and DMSO.
The amount of water in the composition is typically in the raage of about 20 to about
60%, and alcohols typically about 80% to about 40%. The ethanol and the propylene
glycol ere preferably present in a relative weight ratio of about 3:1 to about 0:1.
Preferably, the composition need not be removed after application.
Mucosal Formulations
For mucosally administered antidepressants, administration is via application to
the mucosa of said male as a composition that may include a carrier for facilitating the
application of the antidepressant agent to the mncosa.
Similarly, it will be understood that the compositions for mucosal administration
may be in many forms. Most typically, the invention is formulated as a spray for nasal
administration, although it may be formulated for buccal administration in me form of a
troche or in the form of a suppository for rectal administration. Those skilled in the art
will appreciate that the important consideration is to select the antidepressant, the dosage
and the dosage form in combination to provide a sufficient quantity of antidepressant is
present to induce a degree of anaesthesia in the male genitalia to prevent premature
calculation.
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Nasal formulations include gels, suspension, liposomal dispersions, emulsions or
microamulsions and may be any combination of aqueous and non-aqueous components.
Alternatively, the nasal formulations may be in powdered form, such as microspheres,
liposomes. coated microspheres (for example, such as those with a cellulose or
polysaccharide coating).
The nasal formulations of the present invention may include conventional
additives and excipients, such as buffers, thickening agents, soothing agents, sweeteners
and membrane conditioners or transport agents, antioxidants, preservatives, penetrating
agents and other carriers which will be known by those skilled in the art It is preferably
dispensed via a metered spray vessel. Administering the dose in a metered fashion
enables a use of a defined quantity of the active ingredient involved.
Nasal formulations may typically include water, polyethylene glycols (various
pharmaceutically acceptable PEG's,) glycerine, DMSO, ascorbic acid or ascorbate salts
or bisuifites.
Preferably, the antidepressant in the nasal formulation is present in an amount of
between 0.1 and 1000mg per dose, depending upon the active ingredient used. More
preferably, the dosage will be between 1 and 00rng antidepressant, even more
preferably "between 5 and 25 mg aotidepressant.
Preferably, the dosage is taken nasally just prior to intercourse, between 10 and 30
minutes prior to intercourse, most preferably around 20 minutes prior to intercourse.
The nasal composition may be administered by means of one or two metered doses
shortly before intercourse, or by way of a troche or suppository which are administered
slightly further ahead of time.
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A typical nasal spray of the present invention contains antidepressant (name) such that a
single dose typically delivers from 2 to 50 mg antidepressant (name). The volume of
one actuation of a-metered dose is generally 20 to 500 microlitres.
antidepressant (name) 100mg
Antioxidant 1%
Preservative 0.5%
Dimethyl srulfoxide 0,02%
Purified Water to 100.
Formulation for application to the lungs
Any conventional formulation for administration to the kmgs may be used.
Preferably, this is via inhalation. Apropollant is preferably also included in such
formulations.
The drug may be delivered in the. form of, for example a dry powder, a recognized
drug suspended in a liquefied propellent, or a drug dissolved, either alone or by way of a
cosolvent, in 9 liquefied propellant.
Preferably, the particle size of the dry material is less than l0 microns, and
preferably less than about 5 microns
Aerosols propellants include any agents suitable for medical use provided they are
compatible with the active. They may be, for example, CFC (chlorofluorocarbon) or
HFA (hydrofluoroalkane) propellents.
All types of nebuliser may be used - pressure, powder, metered powder or
Ultrasonic.
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Where the. active antidepressant is dissolved, a cosolvent may be added. A.
suitable cosolveat is, for example, ethanol.
Other ingredients, may be added to the formulations. These may include, for
instance, surface active agents (surfactants). Any suitable Surface active agem may be
used. These may include, for example, oleic acid, sorbitan trioleate and lecithin.
Preferably, the antidepressant is administered in an amount of between 0.1 and
1000mg per metered dose. More preferably, the dosage will be between 1 and l00mg
antidepresant, even more preferably between 5 and 25 mg antidepressarnt.
Results
A range of commonly available antidepressants were prepared and administered
according to the present invention as described above.
All three routes of administration, oral, nasal and a combination of topical and
nasal were found to produce a reduction in premature ejaculation as a whole. Those
sheets taking the antidepiessants by both the nasal and the topically administered
formulations noted particularly good results.
For those patients taking the antidepressants by both routes, it may be
advantageous if the antidepressants were selected from different groups, eg if one was an
SSR1 and the other was a MAO inhibitor, for example.
Antidepressants were administered to a large number of subjects in accordance
with the method, of the present invention. The study involved in excess of 200 patients
in each treatment group. All subjects reported experiencing premature ejaculation prior
to commencing the study. All medicaments were self administered. Topical
administration was to the skin of the glans. Paroxetine, Fluoxetine and Sertraline were
—administered randomly via a mixture of routes.
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Assessment was made by asking patients whether they were satisfied with the
result. Almost all subjects reported an improvement in time to ejaculation. A
combination of nasal and topical seemed to be most satisfactory, in providing the best
result to the largest number of subjects.
While the invention is described with reference to specific embodiments, it will
be understood by those skilled in the art that that variations and modifications may be
made without departing from the inventive concept disclosed herein,
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1. A method of treating premature ejaculation in a male comprising administering
to the male an antidepressant via a route selected from the group consisting of;
i) mucosal administerition-,
ii) administration to the lungs
iii) local administration to at least a part of the male genit&lia and
iv) a combination of two or more of mucosal administration, administration to the lungs
and local administration to at least a part of the male genitalia.
2. A. method according to claim. 1 "wherein the antidepressant is administered prior to
sexual activity
3. A method according to claim 1 or claim 2 wherein the antidepressant is
administered during sexual activity
4. The method according to claim 1 wherein the mucosal administration is by nasal
administration, buccal administration, rectal administration or combinations thereof
5. The method according to claim 1 wherein administration to the lungs is by way
of inhalation.
6. The method according to claim 1 wherein local administration is directly to the
penis.
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7. A. mathod according, to any one of claims 1 to 3 wherein. the antidepressant is
administered by a combination of mucosal adiministration. and local administration.
8. A method according to any one of claims 1 to 3 wherein the antidepressant is
administered by a combination of mucosal administration and administration to the
9. The method according to any one of claims 1 to 3 wherein the antidepressant is
adminisrered by R combination, of local administration and administration to the lungs.
10. The method according to claim 9 wherein local administration is topical
administrationl to the penis and administration to the lungs is nasal administration.
11. The method according to any one of the preceding claims wherein the
antidepressant is administered by a combination of mucosal administration, local
administration and administration to the lungs.
12. The. method according to any one of the preceding claims wherein the
antidepressant is administered in an amount of between 0.1 and 1000 mg per dose.
13. The method according to any one of the preceding claims wherein the
antidepressant is administered in an amount of between 1 and 100 mg per dose
14. The method according to any one of the preceding claims wherein the
antidepressant administered in an amount of between 5 and 25 mg per dose
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15. The method according to claim 1 wherein a single anti depressant or single
combination of antidepressants is administered by two or more routes selected from the
mucosal administration, administration to the lungs and local administration to at least a
part of the male genitalia.
16. The method according to claim 1 wherein two or more different antidepressants or
two or more different combinations of antidepressants are administered by two or more
routes selected from the mucosal administration, administration to the lungs and local
administration to at least apart of the male genitalia.
17. The method according to claim 16 wherein the antidepressant combination
includes serotonin reuptake irhibitor (SSRIs) and a monoamine oxidase inhibitor.
18. The method according to claim 1 wherein the antidepressant is massaged into
the skin of the male genitalia prior to intercourse for about one minute.
19. The method according to claim 18 wherein the antidepressant is massaged into
the skin of the male genitalia about 30 to 60 minutes prior to intercourse;
20. The method according to claim 1 wherein, the antidepressant is taken, nasally
within 30 minutes prior to intercourse.
21. The method according to claim 20 wherein the antidepressant is taken uasally just
prior -to intercourse
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22. The method according to claim 20 or 21 administered nasally by means of one or
two-metered doses shortly before intercourse.
23. The method according to claim 1 wherein the antidepressant is administered by
way of a troche or suppository prior to Intercourse.
24. A method of treating premature ejaculation in a male comprising the step of
administering to the male an antidepressant, wherein the antidepressant is administered
via a route selected from the group consisting of i) nasal administration, ii)
administration to the lungs, iii) buccal administration, iv) administration to the penis,
and v) a combination of two or more of nasal adrninistration, administration to the lungs,
buccal administration and local administration to live penis, thereby to provide a
sufficient degree of anaesthesia to the penis to overcome premature ejaculation,
25. A method of prolonging sexual intercourse involving a male, the method including
the step of administering to the male prior to intercourse an amount of an antidepressatil
effective to delay ejaculation; and wherein the antidepressant is administered via a route
selected, from the group consisting of: mucosal administration, administration to the
longs, topical administration, to the male genitalia, and a combination of two or more of
mucosal administration, administration to the lungs or topical administration to the male
genitalia.
26. A method of prolonging sexual intercourse involving a male and a female, the
method including the step of administering to the male prior to intercourse an amount of
20

an antidepresaant effective to delay ejaculation without anaesthetising the female
genitalia; and wherein the antidepressant is administered via a route selected from the
group consisting of: mucosal administration, administration to the lungs, topical
administration to the male genetalia, and a combination of two or more of mucosal
administration, administration. to the lungs or topical administration to the male
genitalia.
27. A composition for the treatment of premature ejaculation, said composition
comprising an anridepressant formulated for mucosal administration, administration to
the lungs and/or local administration to at least part of the male genetalia.
28. The composition according to claim 27 wherein said antidepressant is selected
from serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors,
moaoamine oxidase inhibitors, norepinephine dopamins reuptake inhibitors, serotonin
antagonist and reuptake inhibitors, norepinephrine antagonist/serotonin antagonists,
synthetically derived phenylpiperazine antidepressants, antagonists of central 12-o2 auto
and heteroadrenoceptors, and mixtures theraof.
29. The composition according to claim 28 wherein said antidepressant is a mixture of
a serotonin reuptake inhibitor and a monoamine oxidases inhibitor.
30. The composition according to claim 29 wherein said serotonin norepinephine
reuptake inhibitor is a bicycle, tricyclic or tetracyclic antidepressant.
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31. The composition according to any one of claims 27 to 30 wherein said
antidepressant is selected. firom paroxetine, fluaxottine, sertraline, citalopram.
hydrobromide fluvoxamine, sertraline, nortriptyline hydrochroide, cloropramine
hydrochloride dothiepin. hydrochloride,, Imipramine hydrochloride, mianserin
hydrochloride, amitriptyline hydrochloride, phenelzine sulphate, tranycypromine
sulphate, isocarboxazid moclobemide, seratonin and/or adrenalin update inhibitors such
as venlafaxine, nefezodone hydtochloride, trazodone, burpropion, mirtazapine, doxspin
hydrochlorids, trimipramine or mixtures thereof.
32. The composition according to claim 31 wherein said antidepressant. is selected
from, paroxetine, fluoxoetins, sextraline or mixtures thereof.
35. The composition according to claim 32 "wherein said paroxetine is formulated as a
hydrochloride or mesyslate.
34. The composition according to any one of claims 27 io 33 including a carrier to
facilitate the administration of the antidepressant.
35. The composition of any one of the preceding claims having a pH of around 7.4.
36. The composition according to any one of claims 27 to 35 formulated for local
administration directly to the penis.
37. The composition according to any one of claims 27 to 36 for local administration
to the penis in the from of a gel, lotion or a powder.
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38. The composition according to claim 37 wherein said powder can be hydrated to
from a gel or Lotion,
39. The composition according to claim 38 wherein said gel is a hydrogel or an
acrylic acid polymer.
40. The composition according to any one of claims 36 to 39 further comprising an
enhancer agent for enhancing the absorption of the antidepressant agent through the
skin.
41. The composition according to claim 40 wherein the enhancer agent is a
cyclodextrin, water, a monohydric alcohol, a polyhydric alcohol
42. The composition according to claim 41 wherein the enhancer is ethanol,
polyethylene glycol and propylene glycol or their mixtures thereof.
43. The composition according to claim 42 comprising:
about 20 to about 60°/o water-
about 80% to about 40% alcohols
1 to 10% Hydroxypropyl-b-cyclodextrin (HPBCD) and wherein antidepressant
agent and the HPBCD are typically present in the composition in a molar ratio of about
1:0.8 to 1:1.4 respectively.
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44. The composition according to claim 43 wherein said HPBCD has a degree of
substitution 5 to 1.
45. The composition according to any one of claims 27 to 44 "wherein the
concentration of the antidepressant is between about 1 to 10% by weight of said
composition.
46. The composition according to claim 45 "wherein the amount is about 3 to 6% by
weight of the composition.
47. The composition according to claim 27 for mucosal administration and Formulated
as a nasal spray, as a troche for bucal administrition or in the form of a suppository DOT
rectal admimstration.
48. The composition according to claim 47 wherein said nasal spray is in the form of
ac aqueous or non-aqueous gel, suspension. liposomal dispersion, emulsion or
microemulsion. or in powdered, microsphere, coated microsphere or liposomal form.
49. The composition according to claim 48 formulated for administrition to the lungs
via inhalation and in the form of a dry powder, a micronized drug suspended in a
liquefied propellant, or a drug dissolved, either; alone or by way of a cosolvent, in a
liquefied propellant.
50. The composition according to claim 49 wherein the particle size of the dry
powder is less than 10 microns.
24

51. The composition according to claim 49 in the form of an aerosol and wherein
said propellant is CFC (chlorofluorocarbon) or UFA (hydrofluoroalkane) propellents.
52. The composition according to claim 49 including a surface active agent selected
from oleic acid, sorbitan trioleate, lecithin and teir mixtures thereof.
53. A kit comprising an antidepressant formulated for nasal administration and an
antidepressant formulated for local administration to at least part of the male genitalia.
54. A kit comprising an antidepressant formulated for administration to the lungs and
an antidepressant formulated for local administration to at least part of the male
genitalia.
55. A. kit comprising an antideptsssant formulated for nasal administration and an
antidepressant formulated for administration to the lungs.
56. A kit comprising an antidepersssant formulated for nasal administration, an
antidepressant formulated for administration.to the lungs and an antidepressant
formulated for local administration to at least gart of the male genitalia.
57. A kir according to any one of claims 29 to 32 wherein said antidepressants axe
selected such that they act synergistically cm administration.

The invention relates to methods and compositions for treating premature ejaculation in a
male or prolonging intercourse comprising administering to the male an antidepressant via a
route selected from the group consisting of mucosal administration (preferably nasal, buccal
or rectal), administration to the lungs (preferably by inhalation), local administration to at
least a part of the male genitalia (applied to the penis far example, in the form of a gel) and
combinations thereof.